Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019.

Aim: The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown.

Effects of Inhibition of Nitric Oxide Synthase on Muscular Arteries During Exercise: Nitric Oxide Does Not Contribute to Vasodilation During Exercise or in Recovery.

Background Basal release of nitric oxide (NO) from the vascular endothelium regulates the tone of muscular arteries and resistance vasculature. Effects of NO on muscular arteries could be particularly important during exercise when shear stress may stimulate increased NO synthesis. Methods and Results We investigated acute effects of NO synthase inhibition on exercise hemodynamics using N-monomethyl-l-arginine (l-NMMA), a nonselective NO synthase -inhibitor.

Blood Pressure in Healthy Humans Is Regulated by Neuronal NO Synthase.

NO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effects on cardiovascular function, but its composite effects on systemic hemodynamics in humans are unknown.

Impaired neuronal nitric oxide synthase-mediated vasodilator responses to mental stress in essential hypertension.

Neuronal NO synthase (nNOS) regulates blood flow in resistance vasculature at rest and during mental stress. To investigate whether nNOS signaling is dysfunctional in essential hypertension, forearm blood flow responses to mental stress were examined in 88 subjects: 48 with essential hypertension (42±14 years; blood pressure, 141±17/85±15 mm Hg; mean±SD) and 40 normotensive controls (38±14 years; 117±13/74±9 mm Hg). A subsample of 34 subjects (17 hypertensive) participated in a single blind 2-phase crossover study, in which placebo or sildenafil 50 mg PO was administered before an intrabrachial artery infusion of the selective nNOS inhibitor S-methyl-l-thiocitrulline (SMTC, 0.

Altered dependence of aortic pulse wave velocity on transmural pressure in hypertension revealing structural change in the aortic wall.

Aortic pulse wave velocity (aPWV), a major prognostic indicator of cardiovascular events, may be augmented in hypertension as a result of the aorta being stretched by a higher distending blood pressure or by a structural change. We used a novel technique to modulate intrathoracic pressure and thus aortic transmural pressure (TMP) to examine the variation of intrathoracic aPWV with TMP in hypertensive (n=20; mean±SD age, 52.1±15.

Dominance of the forward compression wave in determining pulsatile components of blood pressure: similarities between inotropic stimulation and essential hypertension.

Pulsatile components of blood pressure may arise from forward (ventricular generated) or backward wave travel in the arterial tree. The objective of this study was to determine the relative contributions of forward and backward waves to pulsatility. We used wave intensity and wave separation analysis to determine pulsatile components of blood pressure during inotropic and vasopressor stimulation by dobutamine and norepinephrine in normotensive subjects and compared pulse pressure components in hypertensive (mean±SD, 48.

Augmentation pressure is influenced by ventricular contractility/relaxation dynamics: novel mechanism of reduction of pulse pressure by nitrates.

Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively.

Sympathetic activation increases NO release from eNOS but neither eNOS nor nNOS play an essential role in exercise hyperemia in the human forearm.

Nitric oxide (NO) release from endothelial NO synthase (eNOS) and/or neuronal NO synthase (nNOS) could be modulated by sympathetic nerve activity and contribute to increased blood flow after exercise. We examined the effects of brachial-arterial infusion of the nNOS selective inhibitor S-methyl-l-thiocitrulline (SMTC) and the nonselective NOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA) on forearm arm blood flow at rest, during sympathetic activation by lower body negative pressure, and during lower body negative pressure immediately after handgrip exercise. Reduction in forearm blood flow by lower body negative pressure during infusion of SMTC was not significantly different from that during vehicle (-28.

Estimating central systolic blood pressure during oscillometric determination of blood pressure: proof of concept and validation by comparison with intra-aortic pressure recording and arterial tonometry.

Objectives: Central systolic blood pressure is usually estimated by transformation of a peripheral arterial waveform obtained by tonometry and calibrated from conventional measurements of brachial artery blood pressure from a brachial cuff using the oscillometric principle. We investigated whether central blood pressure could be obtained directly from a brachial cuff waveform, allowing the measurement of central blood pressure to be incorporated into the standard oscillometric determination of blood pressure.

Methods: Values of central systolic blood pressure obtained from a brachial cuff waveform were compared with those obtained using a pressure-tipped intra-aortic catheter in 29 individuals undergoing cardiac catheterization.

Estimating central SBP from the peripheral pulse: influence of waveform analysis and calibration error.

Objective: To compare estimation of central cSBP by application of a generalized transfer function (GTF) to a peripheral arterial waveform and from the late systolic shoulder (SBP(2)) of such a waveform and assess errors introduced by noninvasive calibration of the waveform.

Methods: The digital arterial pulse was acquired noninvasively with a servo-controlled finger cuff. A high fidelity pressure tipped catheter was placed in the proximal aortic root.

Differential effects of beta-adrenoreceptor antagonists on central and peripheral blood pressure at rest and during exercise.

Background: Differential effects of beta-adrenoreceptor antagonists (beta-ARB) on central and peripheral blood pressure may relate to change in heart rate and/or vasodilator tone and thus be exaggerated during exercise.

Aims: To examine acute effects of selective and nonselective beta-ARB on central and peripheral blood pressure, cardiac output and peripheral vascular resistance during exercise.

Methods: Healthy volunteers (n= 20, 18 men, 19-54 years) received propranolol 80 mg, bisoprolol 20 mg, and placebo 1 h before bicycle ergometry (50, 75 and 100 W each for 3 min) in a randomized, cross-over study.

Neuronal nitric oxide synthase regulates basal microvascular tone in humans in vivo.

Background: Nitric oxide (NO) has a pivotal role in the regulation of vascular tone and blood flow, with dysfunctional release contributing to disease pathophysiology. These effects have been attributed to NO production by the endothelial NO synthase (eNOS); however, recent evidence suggests that a neuronal NO synthase (nNOS) may also be expressed in arterial vessels.

Methods And Results: We undertook a first-in-humans investigation of the role of nNOS in the local regulation of vascular blood flow in healthy subjects.

Exercise reduces arterial pressure augmentation through vasodilation of muscular arteries in humans.

Exercise markedly influences pulse wave morphology, but the mechanism is unknown. We investigated whether effects of exercise on the arterial pulse result from alterations in stroke volume or pulse wave velocity (PWV)/large artery stiffness or reduction of pressure wave reflection. Healthy subjects (n = 25) performed bicycle ergometry.

Elevation of plasma homocysteine by methionine loading increases the diastolic blood pressure response to exercise.

Objective: Exercise blood pressure is elevated in conditions associated with endothelial dysfunction. To determine whether this is a causal association, we examined the effects of endothelial dysfunction induced by methionine loading, on exercise blood pressure.

Design: Healthy subjects (18-63 years) participated in randomized, double-blind, cross-over studies receiving methionine and placebo on separate occasions before exercise.

Cardiovascular risk factors and endothelial dysfunction.

Endothelial dysfunction is a feature of atherosclerosis and is associated with CHD (coronary heart disease) risk factors. This study aimed to determine the relationship between the degree of endothelial dysfunction and calculated cardiovascular risk. Endothelial function, as determined by the ACh/NP (acetycholine/sodium nitroprusside response) ratio on brachial plethysmography, was compared with cardiovascular risk as calculated from the Framingham, PROCAM (Prospective Cardiovascular Munster) and MRFIT (Multiple Risk Factor Intervention Trial) algorithms in 246 (187 male) patients, including 44 (22%) with established CHD.

Acute haemodynamic effects of lipolysis-induced increase of free fatty acids in healthy men.

Circulating free fatty acids (FFA) are elevated in subjects with insulin resistance and Type II diabetes, and increase during myocardial ischaemia, but their haemodynamic effects are incompletely understood. During an investigation of the effects of FFA on endothelial function, we administered lipid emulsion (150 mg x min(-1) of soybean oil) with heparin (0.2 unit x kg(-1) x min(-1)) intravenously to eight healthy men for 2 h.